Summary of Work: The primary objective of this study is to examine the association between insulin-like growth factor (IGF)-I and two of its binding proteins (IGFBP-4 and IGFBP-5) and bone density of the hip and spine in 100 men and 100 women ages 60 and older from Cycle 6 of the Framingham Offspring Study Osteoporosis Call-back Study. The main hypotheses to be investigated are: 1. IGF-I has a modest direct association with bone mineral density (BMD) of the hip and spine; however, 2. IGFBP-4, which inhibits IGF action, is strongly and inversely correlated with BMD. 3. IGFBP-5, which potentiates IGF-induced bone cell proliferation, is positively correlated with BMD. 4. IGFBP-4 is strongly and positively associated with parathyroid hormone (PTH). Since calcium deficiency is associated with secondary hyperparathyroidism, IGFBP-4 will be increased in calcium deficient women. Assays for PTH and IGFBP-I also will be included, extending the usefulness of these data for investigating the mechanisms underlying age-related changes in bone as well their role in the development of other health conditions in old age. The proposal has been approved by the Review Committee of the Framingham Study and collection of serum and BMD data is currently underway.